The development of new formulations that enhance water solubility and bioavailability of active pharmaceutical ingredients (APIs) is an important area of modern drug delivery, given that a large number of highly active potential drug candidates are relatively hydrophobic in nature. Additionally, oral administration routes are highly preferred, as they lead to increased patient compliance and avoid needles/pain and the need for sterile conditions during formulation manufacture. Numerous types of oral formulations have been proposed in order to overcome the obstacles related to poor bioavailability of hydrophobic APIs. These formulations use (i) micelles, (ii) micro/nano-emulsions, (iii) liposomes, (iv) dendrimers, (v) biodegradable polymer and mesoporous silica nanoparticles, and (vi) water-soluble excipients such as cyclodextrins, among others.
Ibuprofen is a widely available and moderately potent non-steroidal anti-inflammatory drug (NSAID) that has a low systemic toxicity and, unlike some other NSAIDs, such as aspirin, indomethacin and piroxicam, has a relatively low risk of side effects related to gastric damage. This API has been entrapped in a variety of metal organic frameworks (MOFs), including UiO-66 that had been modified with a variety of functional groups resulting in loading ranges from 13 to 36 weight percent (wt. %); MIL-53(Cr) and MIL-53(Fe) that show loading capacities of around 20 wt. %; MIL-101(Cr) and 10% NH2-MIL-101(Cr) with loadings of 46 and 47 wt. %, respectively; and MIL-100 and MIL-101 with ibuprofen loadings of 26 and 58 wt. %, respectively. (See, Cunha, D.; Gaudin, C.; Colinet, I.; Horcajada, P.; Maurin, G.; Serre, C., Rationalization of the entrapping of bioactive molecules into a series of functionalized porous zirconium terephthalate MOFs. J. Mater. Chem. B 2013, 1, 1101-1108; Silva, I. M. P.; Carvalho, M. A.; Oliveira, C. S.; Profirio, D. M.; Ferreira, R. B.; Corbi, P. P.; Formiga, A. L. B., Enhanced performance of a metal-organic framework analogue to MIL-101(Cr) containing amine groups for ibuprofen and nimesulide controlled release. Inorg. Chem. Commun. 2016, 70, 47-50; Horcajada, P.; Serre, C.; Vallet-Regi, M.; Sebban, M.; Taulelle, F.; Ferey, G., Metal-organic frameworks as efficient materials for drug delivery. Angew. Chem. Int. Ed. 2006, 45, 5974-5978; and Horcajada, P.; Serre, C.; Maurin, G.; Ramsahye, N. A.; Balas, F.; Vallet-Regi, M.; Sebban, M.; Taulelle, F.; Ferey, G., Flexible porous metal-organic frameworks for a controlled drug delivery. J. Am. Chem. Soc. 2008, 130, 6774-6780.) Few studies, however, have considered the use of MOFs in vivo, as a consequence of the toxic nature of the metal ions and/or organic linkers, and the investigations that have considered in vivo activity focus mainly on intraveneous, rather than oral, dosing as a result of the poor water-solubility of the MOFs that were used.